Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMIFA0L)

• Drug Name: APG-115 Drug Info
• Synonyms: 15Qau0SI9J; 15QAU0SI9J; UNII-15QAU0SI9J; 1818393-16-6; APG 115 [WHO-DD]; SCHEMBL17189805; Bicyclo(2.2.2)octane-1-carboxylic acid, 4-((((3'R,4'S,5'R)-6''-chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-1'',2''-dihydro-2''-oxodispiro(cyclohexane-1,2'-pyrrolidine-3',3''-(3H)indol)-5'-yl)carbonyl)amino)-

Indication

Disease Entry	ICD 11	Status	REF
Prolymphocytic leukaemia	2A82.1	Phase 2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

• Cross-matching ID:
  PubChem CID: 91972012
  CAS Number: CAS 1818393-16-6
  TTD Drug ID: DMIFA0L

Molecule-Related Drug Atlas

Drug(s) Targeting Ubiquitin-protein ligase E3 Mdm2 (MDM2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RG7388	DMF5GZI	Acute myeloid leukaemia	2A60	Phase 3	[3]
ALRN-6924	DMLBWT1	Haematological malignancy	2B33.Y	Phase 2	[2]
AMG 232	DM65PTO	Merkel cell carcinoma	2C34	Phase 2	[4]
ASTX295	DM9EM5G	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[5]
HDM201	DMVRTCW	Haematological malignancy	2B33.Y	Phase 1	[2]
DS-3032	DMA2B5Y	Haematological malignancy	2B33.Y	Phase 1	[6]
RG7775	DMXBS6U	Acute myeloid leukaemia	2A60	Phase 1	[7]
JNJ-26854165	DMNSJ3C	Non-small-cell lung cancer	2C25.Y	Phase 1	[8]
BI 907828	DM2Z4YQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
MI-219	DM196LK	Triple negative breast cancer	2C60-2C65	Investigative	[10]

Drug(s) Targeting Cellular tumor antigen p53 (TP53)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Contusugene ladenovec	DMN9ETB	Oral cancer	2B6E	Phase 3	[11]
QPI-1002	DMDU5Y2	Renal transplantation	NE84	Phase 3	[12]
Thymoquinone	DMVDTR2	Polycystic ovarian syndrome	5A80.1	Phase 2/3	[13]
SGT-53	DMLYIPA	Pancreatic cancer	2C10	Phase 2	[14]
APR-246	DMNFADH	Ovarian cancer	2C73	Phase 2	[15]
Ad-p53	DMJSWXL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[16]
Kevetrin	DMFO6MH	Ovarian cancer	2C73	Phase 2	[2]
INGN-225	DMF7J6D	Head and neck cancer	2D42	Phase 2	[17]
ALT-801	DM9KL7P	Acute myeloid leukaemia	2A60	Phase 2	[18]
ISA-P53-01	DMQ5EYJ	Colorectal cancer	2B91.Z	Phase 1/2	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cellular tumor antigen p53 (TP53)	TT7SBF5	P53_HUMAN	Inhibitor	[2]
Ubiquitin-protein ligase E3 Mdm2 (MDM2)	TT08GJW	MDM2_HUMAN	Inhibitor	[2]

References

• [1] ClinicalTrials.gov (NCT04496349) A Study Evaluating APG-115 as a Single Agent or in Combination With APG-2575 in Subjects With T-PLL. U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Pre-clinical evaluation of the MDM2-p53 antagonist RG7388 alone and in combination with chemotherapy in neuroblastoma. Oncotarget. 2015 Apr 30;6(12):10207-21.
• [4] Discovery of a small molecule MDM2 inhibitor (AMG 232) for treating cancer. J Med Chem. 2014 Aug 14;57(15):6332-41.
• [5] Clinical pipeline report, company report or official report of Astex Pharmaceuticals.
• [6] Drugging the p53 pathway: understanding the route to clinical efficacy. Nat Rev Drug Discov. 2014 Mar;13(3):217-36.
• [7] Phase I clinical trail of RG7775 for treating Acute myelogenous leukemia. Roche.
• [8] Serdemetan antagonizes the Mdm2-HIF1alpha axis leading to decreased levels of glycolytic enzymes. PLoS One. 2013 Sep 6;8(9):e74741.
• [9] MDM2 inhibition: an important step forward in cancer therapy. Leukemia. 2020 Nov;34(11):2858-2874.
• [10] MI-219-zinc combination: a new paradigm in MDM2 inhibitor-based therapy. Oncogene. 2011 Jan 6;30(1):117-26.
• [11] A review of contusugene ladenovec (Advexin) p53 therapy. Curr Opin Mol Ther. 2009 Feb;11(1):54-61.
• [12] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [13] Apoptosis as a mechanism for the treatment of adult T cell leukemia: promising drugs from benchside to bedside. Drug Discov Today. 2020 Jul;25(7):1189-1197.
• [14] Transferrin receptor targeting nanomedicine delivering wild-type p53 gene sensitizes pancreatic cancer to gemcitabine therapy. Cancer Gene Ther. 2013 Apr;20(4):222-8.
• [15] APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a dedicated NADPH oxidase. Cell Death Dis. 2013 Oct 24;4:e881.
• [16] Assessment of p53 gene transfer and biological activities in a clinical study of adenovirus-p53 gene therapy for recurrent ovarian cancer. Cancer Gene Ther. 2003 Mar;10(3):224-38.
• [17] INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect. Expert Opin Biol Ther. 2010 Jun;10(6):983-91.
• [18] Phase I trial of ALT-801, an interleukin-2/T-cell receptor fusion protein targeting p53 (aa264-272)/HLA-A*0201 complex, in patients with advanced malignancies. Clin Cancer Res. 2011 Dec 15;17(24):7765-75.
• [19] WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting.